Structural insights into the signal transduction mechanism of the K(+)-sensing two-component system KdpDE.
Structural insights into the signal transduction mechanism of the K(+)-sensing two-component system KdpDE.
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K( ) 传感二元系统 KdpDE 信号转导机制的结构见解。
DOI：
10.1126/scisignal.aaz2970
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发表时间：
2020
影响因子：
7.3
通讯作者：
Han Aidong
中科院分区：
文献类型：
--
作者：
Xie Mingquan;Wu Mengyuan;Han Aidong
双组分系统（TCSs）由组氨酸激酶（HK）传感器和反应调节因子（RR）组成，是细菌快速感知和响应各种环境信号的重要系统。HKs和RRs通常作为同源对发挥作用，仅在转导信号时相互作用。TCS中的精确信号转导依赖于RR的受体结构域（RD）和HK的二聚化和组氨酸磷酸化结构域（DHp）之间的特定相互作用。在这里，我们确定了KdpDE的复杂结构，这是一种由HK KdpD和RR KdpE组成的TCS，负责K+的动态平衡。KdpE的RD和DNA结合域（DBD）都与KdpD相互作用。虽然KdpE的RD和KdpD的DHp有助于结合特异性，但DBD介导了与KdpD的催化atp结合（CA）结构域的独特相互作用，这对于kdpde介导的信号转导是必不可少的。此外，DBD-CA界面与DBD-DNA复合物的界面在很大程度上重叠，导致KdpD及其靶启动子以KdpE磷酸化依赖的方式相互竞争。此外，CA结构域扩展的c端尾部对于稳定与KdpDE的相互作用和信号转导至关重要。总之，这些数据为特定的KdpD和KdpE相互作用提供了分子基础，KdpD和KdpE相互作用在该TCS的有效信号转导和转录调节中起关键作用。
Two-component systems (TCSs), which consist of a histidine kinase (HK) sensor and a response regulator (RR), are important for bacteria to quickly sense and respond to various environmental signals. HKs and RRs typically function as a cognate pair, interacting only with one another to transduce signaling. Precise signal transduction in a TCS depends on the specific interactions between the receiver domain (RD) of the RR and the dimerization and histidine phosphorylation domain (DHp) of the HK. Here, we determined the complex structure of KdpDE, a TCS consisting of the HK KdpD and the RR KdpE, which is responsible for K+homeostasis. Both the RD and the DNA binding domain (DBD) of KdpE interacted with KdpD. Although the RD of KdpE and the DHp of KdpD contributed to binding specificity, the DBD mediated a distinct interaction with the catalytic ATP-binding (CA) domain of KdpD that was indispensable for KdpDE-mediated signal transduction. Moreover, the DBD-CA interface largely overlapped with that of the DBD-DNA complex, leading to competition between KdpD and its target promoter in a KdpE phosphorylation–dependent manner. In addition, the extended C-terminal tail of the CA domain was critical for stabilizing the interaction with KdpDE and for signal transduction. Together, these data provide a molecular basis for specific KdpD and KdpE interactions that play key roles in efficient signal transduction and transcriptional regulation by this TCS.